The overall aim is to develop deoxynucleoside analogs for the treatment of patients with cancer. This includes the study of the mechanisms of action and resistance as well as the exploration of novel strategies to develop new nucleoside analogs with unique properties. In this application, we will focus on the study of the antitumor action of a novel L-nucleoside analog, L(-)dioxolane cytidine (L(-)OddC) discovered in this laboratory. This is based on the study section's recommendation. The Specific Aims are listed: A. Study the effect of nucleoside transport inhibitors on the uptake of L(-)OddC B. Study the intracellular metabolism of L(-)OddC C. Examine the interaction of L(-)OddC and its metabolites with relevant human enzymes D. Examine the antitumor activity of L(-)OddC against human tumor in nude mouse models In addition, we will continue to collaborate with and to serve as a resource to medicinal chemistry laboratories which share common related interests. This proposed study should provide information not only in terms of new drug discovery, but also some basic knowledge regarding the biochemical pharmacology of deoxynucleosides.